Cobalt-Catalyzed Regioselective Ortho C(sp²)-H Bond Nitration of Aromatics through Proton-Coupled Electron Transfer Assistance

Abstract

A cobalt-catalyzed proton-coupled electron transfer (PCET) mediated regioselective ortho-specific nitration of aromatic C(sp)-H bonds using chelation-assisted removable vicinal diamine directing groups was developed. The reaction proceeded under mild conditions in the presence of Co(OAc)·4HO as the catalyst with AgNO utilized as the nitro source as well as terminal oxidant in the presence of O as an external oxidant. No external base or additives were required for this process. Controlled experiments and mechanistic investigations with DFT calculations revealed that the reaction proceeds through a PCET promoted nitro functional group transfer pathway. Moreover, the produced compounds are valuable and pharmaceutically quite relevant.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…While Pd catalysis on N -(2-pyrimidinyl)anilines using K 2 S 2 O 8 as oxidant resulted in regioisomeric mixtures in meta -substituted anilines ( Scheme 147F ), 881 this was not observed on the N -(2-pyridinyl) analogues using aerobic Co catalysis ( Scheme 147H ). 882 Noteworthy in this case is also the range of other N-linked heterocycles effective in the reaction, including pyrimidine, quinolines, pyridazine and benzothiazole. Also two different cleavage protocols were reported, leading to either the o -nitroaniline or the o -phenylenediamines.…”

“…Also two different cleavage protocols were reported, leading to either the o -nitroaniline or the o -phenylenediamines. 882 Finally, Schnürch reported the alkylation of benzylic C(sp 3 )–H bonds in N -(2-pyridinyl)benzylamines using Rh catalysis and tetraalkylammonium halides as terminal olefins surrogates ( Scheme 147I ). 883 To our knowledge this is the only case of C(sp 3 )–H functionalisation with this DG type.…”

Synthetic Protocols for Aromatic Nitration: A Review

“…A comparative study by authors shows that 70 % yield is obtained when the reaction is performed without the use of any external additives. This turns out that AgNO 2 acts as a nitro source as well as an oxidant and proves to be the best system in terms of yield [35] …”

Mild Nitration of Pyrazolin‐5‐ones by a Combination of Fe(NO3)3 and NaNO2: Discovery of a New Readily Available Class of Fungicides, 4‐Nitropyrazolin‐5‐ones

“…Therefore, in recent years, great effort has been made to develop systems that generateN O 2 in situ. Nitrates and nitrites, such as (NH 4 ) 2 Ce(NO 3 ) 6 , [2] Cu(NO 3 ) 2 , [3][4][5] AgNO 3 , [6] Mg(NO 3 ) 2 , [7] Fe(NO 3 ) 3 ·9H 2 O, [8][9][10][11][12][13][14][15][16][17][18][19] tBuONO, [20][21][22][23][24][25] NaNO 2 , [26][27][28][29] and AgNO 2 , [30][31][32] are available and convenient nitrating agents and precursors of NO 2 ;F e(NO 3 ) 3 ·9H 2 Oh as foundt he widest applicationi nn itration reactions due to its low toxicity, availability,a nd low temperature of decomposition in which NO 2 is released. [8][9][10][11][12][13][14][15][16][17][18][19]33] Recently,G ao and Chandrasekharam and their co-workers reported the ortho-nitration of N-acylanilinesb y Fe(NO 3 ) 3 ·9H 2 O [13,<...>…”

“…Nitrogen dioxide (NO 2 ) is one of the most simple and effective nitrating agents, but it is not convenient in operation nor in storage due to its volatility, toxicity, and corrosive properties. Therefore, in recent years, great effort has been made to develop systems that generate NO 2 in situ . Nitrates and nitrites, such as (NH 4 ) 2 Ce(NO 3 ) 6 , Cu(NO 3 ) 2 , AgNO 3 , Mg(NO 3 ) 2 , Fe(NO 3 ) 3 ⋅ 9H 2 O, t BuONO, NaNO 2 , and AgNO 2 , are available and convenient nitrating agents and precursors of NO 2 ; Fe(NO 3 ) 3 ⋅ 9H 2 O has found the widest application in nitration reactions due to its low toxicity, availability, and low temperature of decomposition in which NO 2 is released …”